Carbohydrate metabolism may play an important role in maintaining cell homeostasis in bivalves. In the present study, the temporal variations in immune and carbohydrate metabolism parameters of Zhikong scallop Chlamys farreri under an acute Vibrio anguillarum challenge were investigated in order to better understand the energetic mechanisms of scallop immune defense. After bacterial challenge, reactive oxygen species, total antioxidant capacity, acid phosphatase activity, and transcripts of peptidoglycan recognition protein and heat-shock protein 70 in the hemolymph of scallops increased substantially within 96 h. By contrast, the significantly increased malondialdehyde content was observed in the serum of challenged scallops. As far as carbohydrate metabolism was concerned, the expression levels of hexokinase, isocitrate dehydrogenase, and N-acetylglucosaminyltransferase VI in hemocytes of challenged scallops were significantly up-regulated within 192 h. At 192 h, the electron transport system budgets were significantly higher, while the glycogen contents were significantly lower in soft tissues of challenged scallops as compared to those of control. Moreover, the significantly increased glucose content concomitant with significantly up-regulated expressions of sodium glucose transporter 1 and glucose-regulated protein 78 was observed in the hemolymph at 24 h after challenge. The above results demonstrated that bacterial challenge could induce acute immune responses and cause oxidative stress in scallops. During the bacterial stress period, scallops utilized glucose via anaerobic glycolysis and aerobic oxidation to meet the overall cost of immune response. Also, scallops might rely upon the metabolic pathways of glycogen degradation and gluconeogenesis to maintain glucose homeostasis in hemolymph.